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Ann Thorac Surg 2007;83:231-234
© 2007 The Society of Thoracic Surgeons
a New Drugs Development Unit, Department of Medicine, European Institute of Oncology, Milan, Italy
b Radiation Therapy Division, European Institute of Oncology, Milan, Italy
c Thoracic Surgery Division, European Institute of Oncology, Milan, Italy
d Nuclear Medicine Division, European Institute of Oncology, Milan, Italy
e University of Milan, School of Medicine, Milan, Italy
Accepted for publication August 8, 2006.
* Address correspondence to Dr De Pas, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy (Email: tommaso.de-pas{at}ieo.it).
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Abstract |
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 Top Abstract IntroductionMaterial and MethodsResultsCommentReferences |
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METHODS: We examined the database of all patients who underwent surgery for primary non–small cell lung cancer in our institute. The criteria required for inclusion in this analysis were diagnosis of non–small cell lung cancer with synchronous hematogenous solitary metastasis by staging workup with total body computed tomography scan and brain magnetic resonance if indicated, total body positron emission tomography scan, radical surgery for the primary tumors, local treatment of the solitary metastasis, and systemic chemotherapy administration.
RESULTS: We analyzed the data from 1,509 patients treated from January 2000 to December 2005: 10 patients (0.7%) satisfied the selection criteria. The median overall survival was 26 months, and the median time to progression was 20 months; 6 patients were alive at the time of analysis, with a median follow-up of 30 months. Four patients were tumor progression–free after 9, 18, 23, and 32 months from the start of their treatment.
CONCLUSIONS: The presentation of non–small cell lung cancer with a synchronous hematogenous solitary metastasis identified by [18F]fluorodeoxyglucose positron emission tomography containing complete staging workup is extremely rare. This subset of patients can achieve long-term survival after a multidisciplinary treatment approach.
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Introduction |
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Few reports of combined resection of the primary tumor and local treatment of the distant metastasis are available, and no definitive guidelines exist to assist clinical decision-making. In recent years, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) has emerged as a major component of functional imaging in the diagnosis and management of lung cancer, and recently it has acquired an established role in NSCLC staging.
In our institute, spiral computed tomography (CT) and FDG-PET scans have been routinely used in the workup of patients with localized NSCLC for about 5 years. Even with this workup, the number of patients with a synchronous single distant metastasis from NSCLC was very rare. Nevertheless, it can be hypothesized that this subset of NSCLC patients could represent a well-defined population that benefits from a more satisfactory outcome than the same population staged without FDG-PET. According to this hypothesis, we explored the outcome of the patients who underwent systemic chemotherapy, radical surgery for primary tumors, and local treatment of solitary metastasis.
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Material and Methods |
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The primary objectives of the analysis were time to progression (TTP) and overall survival (OS), evaluated by a Kaplan–Meyer analysis. Time to progression was defined as being the period from the start of the treatment to the date of objective progression or death before objective progression. Overall survival was defined as being the period from the start of the treatment to the date of death.
Our ethical committee was informed of the study and gave their approval for publication. All patients gave their informed consent for the utilization of data for scientific purposes.
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Results |
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TopAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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Patient Characteristics
Patient characteristic are reported in Table 1. The sites of metastatic disease were brain (6 patients), adrenal gland (2 patients), and bone (2 patients). Brain metastases were symptomatic in 3 of the 6 patients evaluated. Both patients with adrenal metastases suffered from thoracic pain; 1 of the 2 patients with bone metastases experienced pain at the site of metastases. Four patients were asymptomatic at the time of diagnosis.
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The Eastern Cooperative Oncology Group (ECOG) performance status was reported in 8 patients: it was 0 to 1 in 6 patients and 2 in 2 patients.
Lung Cancer Characteristics
Seven patients underwent surgery after induction chemotherapy, and 3 patients were operated on immediately. The histotypes were adenocarcinoma (8 patients), large cell carcinoma (1 patient), and squamous cell carcinoma (1 patient). The pathologic stages of NSCLC at the time of surgery were Ib (3 patients), IIIa pN2 (4 patients), IIIb (T4 multifocal N1; 1 patient), and ypT0 ypN0 (1 patient); 1 patient was staged ypT2 ypNx because no mediastinal node dissection was performed.
Three of four patients with N2 disease exhibited occult mediastinal involvement; 1 patient was diagnosed with a clinical N2 disease, confirmed by a pretreatment mediastinoscopy. Despite the pathologic confirmation of N2 involvement, the patient (Table 1, patient 9) underwent a multidisciplinary treatment (systemic chemotherapy, radical surgery for the primary tumor, stereotactic irradiation of brain metastasis) in concordance with the patient’s request, and after a major tumor response to induction chemotherapy was observed.
Treatments
All patients received systemic chemotherapy, radical surgery of the primary tumor, and local treatment of the solitary metastasis.
Chemotherapy
Systemic chemotherapy consisted of cisplatin combined with gemcitabine (8 patients) or with vinorelbine (2 patients) for a median of four cycles (range, three to six). Clinical response to chemotherapy was assessable in 7 patients (2 patients received postoperative treatment; for 1 patient no data were available): 6 patients responded (partial or minor response according to RECIST criteria), and 1 patient had a stable disease. One patient, treated with four cycles of cisplatin plus gemcitabine, obtained complete pathologic remission. None of the patients interrupted chemotherapy because of toxicity.
Surgery
Surgical procedures for primary tumors were lobectomy with radical mediastinal node dissection (8 patients), left pneumonectomy (1 patient), and wedge resection (1 patient). Lobectomy procedures were right upper lobectomy (3 patients), right lower lobectomy (3 patients), left upper lobectomy (1 patient), and left lower lobectomy (1patient). No occurrence of surgery-related death was reported.
Treatment of Metastases
Brain metastases were present in 6 patients and were treated with whole-brain irradiation (1 patient), stereotactic irradiation (4 patients), and surgical metastasectomy followed by stereotactic irradiation (1 patient). Two patients exhibited single bone metastases: both received irradiation treatment, preceded by an incomplete surgical excision in 1 patient. Adrenal metastases were treated with adrenalectomy (1 patient) and radiofrequency tumor ablation (1 patient).
Outcome
The median follow-up was 30 months. The median overall survival and the median time to progression were 26.1 (95% confidence interval, 19.4 to 32.7) and 20.6 (95% confidence interval, 13.5 to 27.6) months, respectively.
At the time of analysis, 6 patients were alive whereas 4 were deceased. With a median follow-up of the 6 surviving patients of 30 (range, 9 to 33) months, 5 patients survived greater than 15 months. Four patients were tumor progression-free after 9, 18, 23, and 32 months after initiating treatment.
Four of six patients with recurring disease experienced the first relapse in sites other than the original site of metastasis: multiple lung lesions (2 patients), abdominal nodes (1 patient), and multiple brain lesions (1 patient).
Two patients experienced the first relapse in the original site of metastasis (brain lesions) and were treated with stereotactic radiotherapy: 1 patient later exhibited distant metastases, the other is still alive and 30 months after initiating treatment, exhibits no ulterior tumor progression.
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Comment |
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The outcome was favorable for the 10 patients included in this analysis. The median overall survival was 26 months, and the median time to progression was 20 months; 6 patients were alive at the time of analysis, with a median follow-up of 30 months. Four patients were tumor progression-free after 9, 18, 23, and 32 months after initiating treatment.
The retrospective methodology of our study as well as the obvious bias in selecting patients appropriate for this multidisciplinary treatment approach does not allow the assessment of the impact of the treatment itself. However, our results are consistent with previous data published in past and recent publications addressing the management of lung cancer with solitary brain or adrenal metastases. One of these, a retrospective review of the memorial Sloan-Kettering Cancer Center experience, suggested that the median survival time of patients suffering from adrenal metastases was 31 months when treated with chemotherapy and surgical resection of all afflicted sites. Moreover, in a prospective trial from October 1992 through February 1999, of the 23 patients diagnosed with NSCLC with a solitary synchronous metastasis, only 12 patients completed the planned treatment with systemic chemotherapy and surgical resection of the primary tumor and metastasis. The observed median survival time for all patients included in the study was 11 months, with 3 patients obtaining long-term disease-free survival [1].
Given that our therapeutic guidelines were based on using a multidisciplinary approach for the treatment of all eligible patients diagnosed with NSCLC and synchronous hematogenous single distant metastasis, no alternative group of patients with similar tumor configurations is available for a confrontation analysis of outcome. Furthermore, even if such a group existed, the rarity of this aforementioned disease and the consequentially small number of afflicted patients would not permit a statistically powered comparison. In fact, we found that NSCLC with solitary hematogenous metastases identified by FDG-PET staging was extremely rare. The 1,509 operable cases that we analyzed represent a subset of all the patients referred to our institute for NSCLC. Of this subset of patients, less than 1% satisfied the criteria required for our analysis. This observation is consistent with the proven role of PET in improving the staging of NSCLC and the localization of undetected metastases, as has already been demonstrated [2].
The low incidence of the presentation of this disease is of major interest. Most previous reports regard patients with both synchronous and metachronous solitary metastases or do not report the total number of patients screened in the published analysis [1–7], making it extremely difficult to execute a comparison analysis. The reported incidence of NSCLC with solitary, synchronous, or metachronous distant metastases was 1% to 3.5%, and 2% for synchronous extracranial metastasis among the 358 patients who underwent radical surgery for NSCLC [6].
In conclusion, the condition of NSCLC with solitary hematogenous metastases identified by an FDG-PET containing complete staging is extremely rare. With a multidisciplinary treatment approach, this subset of patients may obtain long-term survival. The FDG-PET scan is recommended to help screen out patients with NSCLC who are erroneously diagnosed with single metastasis, possibly sparing them unnecessary or overaggressive treatment.
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References |
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